Hostettler Katrin E, Gazdhar Amiq, Khan Petra, Savic Spasenija, Tamo Luca, Lardinois Didier, Roth Michael, Tamm Michael, Geiser Thomas
Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Clinics of Respiratory Medicine, University Hospital Basel, University of Basel, Basel, Switzerland.
PLoS One. 2017 Aug 21;12(8):e0181946. doi: 10.1371/journal.pone.0181946. eCollection 2017.
Stem cells have been identified in the human lung; however, their role in lung disease is not clear. We aimed to isolate mesenchymal stem cells (MSC) from human lung tissue and to study their in vitro properties.
MSC were cultured from lung tissue obtained from patients with fibrotic lung diseases (n = 17), from emphysema (n = 12), and normal lungs (n = 3). Immunofluorescence stainings were used to characterize MSC. The effect of MSC-conditioned media (MSC-CM) on fibroblast proliferation and on lung epithelial wound repair was studied.
Expression of CD44, CD90, and CD105 characterized the cells as MSC. Moreover, the cells stained positive for the pluripotency markers Oct3/4 and Nanog. Positive co-stainings of chemokine receptor type 4 (CXCR4) with CD44, CD90 or CD105 indicated the cells are of bone marrow origin. MSC-CM significantly inhibited the proliferation of lung fibroblasts by 29% (p = 0.0001). Lung epithelial repair was markedly increased in the presence of MSC-CM (+ 32%). Significantly more MSC were obtained from fibrotic lungs than from emphysema or control lungs.
Our study demonstrates enhanced numbers of MSC in fibrotic lung tissue as compared to emphysema and normal lung. The cells inhibit the proliferation of fibroblasts and enhance epithelial repair in vitro. Further in vivo studies are needed to elucidate their potential role in the treatment of lung fibrosis.
人类肺脏中已鉴定出干细胞；然而，它们在肺部疾病中的作用尚不清楚。我们旨在从人肺组织中分离间充质干细胞（MSC）并研究其体外特性。
从患有肺纤维化疾病的患者（n = 17）、肺气肿患者（n = 12）和正常肺脏（n = 3）获取的肺组织中培养MSC。采用免疫荧光染色对MSC进行表征。研究了MSC条件培养基（MSC-CM）对成纤维细胞增殖和肺上皮伤口修复的影响。
CD44、CD90和CD105的表达将这些细胞表征为MSC。此外，这些细胞对多能性标志物Oct3/4和Nanog染色呈阳性。趋化因子受体4型（CXCR4）与CD44、CD90或CD105的阳性共染色表明这些细胞起源于骨髓。MSC-CM显著抑制肺成纤维细胞的增殖达29%（p = 0.0001）。在存在MSC-CM的情况下，肺上皮修复明显增加（增加32%）。从纤维化肺脏中获得的MSC明显多于肺气肿或对照肺脏。
我们的研究表明，与肺气肿和正常肺相比，纤维化肺组织中的MSC数量增加。这些细胞在体外抑制成纤维细胞的增殖并增强上皮修复。需要进一步的体内研究来阐明它们在治疗肺纤维化中的潜在作用。
